User-centred concept design of a blood glucose meter

Tyypin 1 diabetesta sairastavan henkilön sitoutuminen tiheään päivittäiseen verensokeripitoisuuden omaseurantaan on avainasemassa sairauden menestyksekkäälle hallinnalle. Diabeetikon tulisi voida mitata verensokerinsa helposti ja luotettavasti missä ja milloin vain, mutta nykyiset verensokerimittarit eivät kannusta käyttäjiä tiheisiin mittauksiin. Tämä diplomityö kirjoitettiin käyttäjäystävällisen verensokerimittarin tuotekehitysprosessin tueksi. Työssä kartoitettiin kirjallisuudesta verensokerin mittaustekniikoita, selvitettiin kyselytutkimuksella käyttäjien tarpeita ja arvioitiin käyttäjäkeskeisesti markkinoilla olevia liuskakasetillisia verensokerimittareita. Havaittiin, että mittaustekniset haasteet rajoittavat verensokerimittarin toteuttamista käyttäjien tarpeiden mukaisiksi, mutta ohjelmiston ja laitteiston innovatiivisella suunnittelulla voidaan saavuttaa käytettävyysetuja nykyisiin verensokerimittareihin verrattuna. Diplomityön tuloksena muodostetun tuotekonseptin keskeisiä piirteitä ovat älykäs ja joustava käyttöliittymä, joka tukee diabeetikkoa hoitopäätöksissä, ja kätevä muotoilu, joka mahdollistaa mittauksen tekemisen liikkeessä ja ilman laskutilaa. Koska käyttäjät haluavat kuluttaa mahdollisimman vähän aikaa diabeteksen hallintaan, täytyy verensokerimittarin uusien toiminnallisuuksien olla joko aikaa säästäviä tai tuoda muuta ilmeistä lisähyötyä käyttäjälle, kuten helpotusta epävarmuuteen verensokeritason heilahteluista.For the successful management of type 1 diabetes, it is crucial that the patient is committed to frequent self-monitoring of their blood glucose level. A blood glucose measuring device should therefore enable the user to perform measurements anywhere, anytime, but the design of current blood glucose meters does not encourage this. This Master’s Thesis was written to support the product development process of a user-friendly blood glucose meter. Blood glucose measurement technologies were reviewed from the literature, user needs were recognized with a user questionnaire and current commercial all-in-one blood glucose meters were evaluated from a user-centred perspective. It was discovered that a shortage of sufficiently accurate measurement technologies is the main limitation to producing a blood glucose meter that optimally meets user needs. However, with innovative software and hardware design, a usability advantage to current blood glucose meters can be achieved. The main features of the product concept established as a result of this Master’s Thesis include a smart and flexible user interface, which supports the daily decision making of diabetes self-care, and a convenient hardware design, which allows the user to measure their blood glucose on-the-go. As the users want to spend as little time and effort for managing their diabetes as possible, any new functionality in a blood glucose meter design must either save time or provide a significant advantage that the user can appreciate, such as reducing insecurity over blood glucose fluctuations

Relationaalisen asiantuntijuuden rakentuminen varhaiskasvatuksen opettajankoulutuksen ohjatun harjoittelun diskursseissa

The opportunities for the development of expertise created by the cooperation between academic education and working life are the subject of topical discussion. A supervised practicing period for early childhood education teacher-students is a traditional form of co-operation between education and working life and a key context for students learning. Our study examined the possibilities of building the relational expertise of early childhood education teacher students and their supervisors from early childhood education centers and the university during a practicing period. The phenomenon under study was examined through the positions produced for teacher students and supervisors, as well as through the discourses produced about the development of expertise. The data was collected with a questionnaire and discourse analysis was utilized in the analysis. According to the results, teacher students have uncertainty in identifying their expertise. The teachers from early childhood education centers were uniformly positioned as practical experts and the knowledge of the supervisors from university education was produced to manage theoretical knowledge. In addition, three discourses were produced during the practicing period: renewal, need for support, and non-encounter.Akateemisen koulutuksen ja työelämän välisen yhteistyön luomat mahdollisuudet asiantuntijuuden kehittymiselle ovat ajankohtaisen keskustelun kohteena. Varhaiskasvatuksen opiskelijoiden ohjattu harjoittelu on perinteinen koulutuksen ja työelämän yhteistyön muoto ja keskeinen opettajaopiskelijoiden oppimisen konteksti. Tutkimuksessamme tarkasteltiin varhaiskasvatuksen opiskelijoiden sekä päiväkodin ja yliopistokoulutuksen ohjaavien opettajien relationaalisen asiantuntijuuden rakentumisen mahdollisuuksia ohjatun harjoittelun yhteydessä. Tutkittavaa ilmiötä tarkasteltiin opiskelijoiden sekä päiväkodin ja koulutuksen ohjaavien opettajien itselleen ja muille tuotettujen positioiden sekä asiantuntijuuden kehittymisestä tuotettujen diskurssien kautta. Aineisto kerättiin kyselylomakkeella ja analyysissa hyödynnettiin diskurssianalyysia. Tulosten mukaan opiskelijoilla on epävarmuutta oman asiantuntijuutensa tunnistamisessa. Päiväkodin ohjaavat opettajat positioituivat yhtenevästi käytännön osaajiksi ja yliopiston harjoittelua ohjaavien opettajien osaamiseksi tuotettiin teoreettisen tiedon hallinta. Lisäksi varhaiskasvatuksen asiantuntijuuden kehittymiselle harjoittelun aikana tuotettiin uudistumisen, tuen kaipuun ja kohtaamattomuuden diskurssit

The Clinical Spectrum of Missense Mutations of the First Aspartic Acid of cbEGF-like Domains in Fibrillin-1 Including a Recessive Family

Marfan syndrome (MFS) is a dominant disorder with a recognizable phenotype. In most patients with the classical phenotype mutations are found in the fibrillin-1 gene (FBN1) on chromosome 15q21. It is thought that most mutations act in a dominant negative way or through haploinsufficiency. In 9 index cases referred for MFS we detected heterozygous missense mutations in FBN1 predicted to substitute the first aspartic acid of different calcium-binding Epidermal Growth Factor-like (cbEGF) fibrillin-1 domains. A similar mutation was found in homozygous state in 3 cases in a large consanguineous family. Heterozygous carriers of this mutation had no major skeletal, cardiovascular or ophthalmological features of MFS. In the literature 14 other heterozygous missense mutations are described leading to the substitution of the first aspartic acid of a cbEGF domain and resulting in a Marfan phenotype. Our data show that the phenotypic effect of aspartic acid substitutions in the first position of a cbEGF domain can range from asymptomatic to a severe neonatal phenotype. The recessive nature with reduced expression of FBN1 in one of the families suggests a threshold model combined with a mild functional defect of this specific mutation. © 2010 Wiley-Liss, Inc

Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients

Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population

BACKGROUND: Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. METHODOLOGY/PRINCIPAL FINDINGS: This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. CONCLUSION: The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes